Antineoplastic chemotherapy was initially developed using intravenous methods. The arguments in favor of this administration method are:                lesser gastrointestinal toxicity,        total bioavailability, and        potentially lower inter and intra patient exposure variations than with an oral method.        
However, the intravenous method is associated with serious disadvantages that limit its use: the morbidity of vein access, possible complications of central vein channels (infection, thrombosis), the risk of extravasation.
For several years, oral forms of antineoplastic chemotherapy have developed increasingly due to the real benefit possible for the patient. Furthermore, pharmaco-economic considerations that are becoming increasingly important in the choice of therapeutic strategies, are also leading towards the development of oral treatments.
A lot of exploratory work has been carried out on the possible use of molecules intended for the treatment of cancer and administrated by mouth, for former active principles (for example etoposide, cyclophosphamide and idarubicine), new synthetic derivatives of fluoropyridines (for example UFT, capecitabine, S-1), derivatives of platinum (for example JM-216) or Vinca alkaloids (e.g. vinorelbine).
Therefore this invention also concerns stable pharmaceutical compositions for oral administration of vinca alkaloids, and particularly vinorelbine in dispersed form.
Vinorelbine or 3′4′-Didehydro-4′-desoxy-8′-norvincaleucoblastine is an alkaloid derivative of vinca which exerts a cytostatic effect by inhibition of the polymerization of tubulin.
Vinorelbine, and more particularly a salt of vinorelbine, vinorelbine ditartrate, is also active in the treatment of large cell lung cancer and breast cancer. An injectable form was marketed for the first time in France in 1989. It is now marketed throughout the world in the form of a solution to be diluted for perfusion, to a concentration of 10 mg/ml expressed in basic vinorelbine and distributed in flasks with unit volumes of 1 and 5 ml.
More recently, an oral formulation of vinorelbine in solution was developed and put on the market under the name of NAVELBINE Oral® soft capsules. It is in the form of a soft gelatin capsule containing vinorelbine ditartrate and an excipient mix comprising polyethyleneglycol, glycerol, ethanol and water. The average molecular mass of polyethyleneglycol is between 200 and 600: these are liquid polyethyleneglycols such as MACROGOL 400. Unit doses expressed in basic vinorelbine are between 5 mg and 100 mg, and more advantageously equal to 20 mg, 30 mg, 40 mg and 80 mg.
These soft capsules were described in a patent application R. P. Scherer Technologies, Inc. WO 03/101383.